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8:30 am Chair’s Opening Remarks

Investigating Diverse Therapeutic Modalities to Treat Neurodevelopmental Disorders

8:40 am Accelerating Clinical Trials in Rare Diseases by Moving Beyond One Disease at a Time

  • PJ Brookes Program Director, Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health

Synopsis

  • Exploring platform approaches to gene therapies to accelerate therapeutic development for monogenic diseases
  • How much can we push platform capacity of AAV’s?
  • How can we run clinical trials more efficiently?
  • The need to streamline our current approaches and enable a more scalable, and inherently patient-centric approach
  • Evaluating broader collaborative approaches that the NIH are taking to accelerate gene therapy clinical trials

9:10 am Rett Syndrome as a Case Example of Gene Dosage Sensitivity: miRARE-mediated Feedback Regulation as a Possible Solution

  • Steven Gray Associate Professor, University of Texas Southwestern Medical Center

Synopsis

  • Overview of AAV9 gene therapy
  • Is AAV9 good enough?
  • When building your AAV, how will you control dosage?
  • Evaluating dose sensitivity strategies and efficacy data using Rett syndrome as a case study
  • What is the best formulation to yield better biodistribution?

9:40 am Utilizing Precision Genetic Medicine to Treat Rare Neurodevelopmental Diseases: Focusing on Rett Syndrome

Synopsis

  • Requirement of clear understanding of target engagement
  • Importance of predictive biomarker of response correlating with efficacy
  • Relevance of appropriate efficacy endpoints

10:10 am Speed Networking

10:40 am Panel Discussion – Diving into Specific Therapeutic Modalities

  • PJ Brookes Program Director, Office of Rare Diseases Research, National Center for Advancing Translational Sciences, National Institutes of Health
  • Steven Gray Associate Professor, University of Texas Southwestern Medical Center
  • Barbara Bailus Assistant Professor of Genetics, Keck Graduate Institute

Synopsis

  • Advantages and disadvantages across small molecules, gene therapy, antisense oligonucleotides, gene replacement, stem cell therapy and hybrid strategies
  • With each modality, what needs to happen before the trial, concurrently with the trial and after?
  • What’s the longevity of these approaches?
  • What are the knock on effects of taking these genes out?
  • What is a good candidate for a gene altering therapy or a disease modifying therapy?
  • What limitations might we face due to public policy?

11:10 am Therapeutic Strategies for Angelman syndrome

Synopsis

  • Unique genetic mechanism underlying Angelman Syndrome informs multiple therapeutic approaches
  • Learnings from ASOs are being incorporated into next-generation gene editing approaches
  • Key considerations for success with gene therapy and gene editing approaches

11:40 am Developing STK-001: An Oligonucleotide Treatment for Dravet Syndrome, Treatment Beyond Seizure Control

Synopsis

  • Exploring the clinical trial design and global expansion for STK-001
  • Assessing the enrolment, dosing strategies and secondary endpoints chosen
  • Evaluating safety and pharmacokinetic data from the SAD portion of the MONARCH study

12:10 pm Electrophysiological & Sleep Abnormalities in Angelman Syndrome

Synopsis

  • Awake EEG delta-band activity correlates with symptom severity crosssectional and longitudinally
  • The observational study FREESIAS investigated sleep in AS and controls
    over the course of one year by a multi-modal approach
  • Sleep diary reveals sleep impairment in AS compared to controls,
    especially visible in variability of sleep over time.
  • Sleep mat provides daily, effortless and objective sleep metrics that
    correlate well with parent reports (e.g. sleep diary, SNAKE)
  • Although sleep scoring is complicated by the high delta-band
    activity observed in Angelman syndrome, overnight PSG recordings
    reveals abnormal sleep physiology with high between-patient
    variability

12:40 pm Live Q&A Session with Your Expert Speakers

1:00 pm Networking Lunch

2:00 pm Regulatory Considerations for Neurodevelopmental Assessments

  • Naomi Knoble Reviewer, Division of Clinical Outcome Assessment, US Food & Drug Administration

Synopsis

  • Reviewing regulatory guidance and good research practices to inform
    clinical outcome assessment measurement in clinical trials
  • Identifying challenges and solutions for the implementation of
    neurodevelopmental assessments to aid clinical medical product
    development trials
  • Discussing potential solutions for neurodevelopmental test score
    selection to identify outstanding methodological evidence for
    neurodevelopmental assessments in clinical trials and opportunities for
    pre-competitive collaboration

2:30 pm Developing GTX-102, an Investigational Antisense Oligonucleotide Designed to Target & Inhibit Expression of UBE3A-AS

Synopsis

  • Exploring clinical activity and evaluating the safety, tolerability, and
    plasma and cerebrospinal fluid concentrations of GTX-102 in paediatric
    patients
  • Discussing the eligibility criteria, dosage and modified trial design
    chosen in this clinical trial to help inform further clinical trials
  • Investigate the clinical trial outcomes on patients with Angelman’s
    Syndrome to help inform therapeutic development

3:00 pm Exploring the Pre-Clinical Stage of Development for UX055, an Investigational Gene Therapy Program for CDD

Synopsis

  • How this is designed to deliver a fully functioning copy of the human CDKL5 gene to neurons with the goal for those neurons to read the new gene and produce functional CDKL5 protein
  • Discovering how AAV9/hCDKL5 delivery to cerebrospinal fluid of juvenile CDKL5-deficient mice improves learning and memory and motor function in adult mice
  • Results from key efficacy studies in a model of human neurons derived from induced pluripotent stem cells (iPSCs) from CDD patients

3:30 pm Preclinical Development of a Cross-Correcting Gene Therapy for CDKL5 Deficiency Disorder

  • Brian Ranes Principal Investigator, Imaging Core , Amicus Therapeutics

Synopsis

  • Exploring preclinical research and development of gene therapies for the treatment of rare neurodevelopmental disorders, focusing on CDKL5
  • Evaluating pre-clinical data and efficacy in mice
  • Early developmental EEG and seizure phenotypes

4:00 pm Live Q&A Session with Your Expert Speakers

  • Sharyl Fyffe-Maricich Executive Director, Molecular & Cell Biology, Research, Ultragenyx
  • Brian Ranes Principal Investigator, Imaging Core , Amicus Therapeutics
  • Scott Stromatt Chief Medical Officer, GeneTx Biotherapeutics
  • Naomi Knoble Reviewer, Division of Clinical Outcome Assessment, US Food & Drug Administration

4:20 pm Afternoon Refreshments

4:50 pm Gene Activation Approaches in Prader-Willi Syndrome

  • Theresa Strong Director of Research Programs, Foundation for Prader- Willi Research (FPWR)

Synopsis

  • Advancing the understanding of innovative gene activation strategies for PWS – critical research questions
  • Diving into limitations and differences across CRISPR-based activation, designer transcriptional factor molecules and small molecules
  • Considerations around clinical trial design and challenges of moving these programs forward

5:20 pm Exploring DCCR as an Important Therapeutic Option for PWS

Synopsis

  • Elucidating the mechanism of action for the DCCR development program for PWS
  • Evaluating the dose rationale for future studies
  • Regulatory back and forth for advancing phase 3 program, outcomes and key learnings

5:50 pm Live Q&A Session with Your Expert Speakers

  • Theresa Strong Director of Research Programs, Foundation for Prader- Willi Research (FPWR)
  • Anish Bhatnagar Chief Executive Officer, Soleno Therapeutics

6:00 pm Chair’s Closing Remarks